title: [Celecoxib enhances chemosensitivity of oral cancer cells by blocking cell cycle progression in vitro].
abstract: OBJECTIVE
  To investigate the effect of celecoxib in enhancing the chemosensitivity of oral cancer cells and the correlation of this effect with cell cycle arrest.
  
  
  METHODS
  KB/VCR cell line was treated with celecoxib (10, 20, 40, and 80 µmol/L) and/or VCR (0.375, 0.75, 1.5, and 3 µmol/L), and the growth inhibition rates of KB/VCR cells were assessed with MTT assay. Flow cytometry was employed to analyze the distribution of cell cycle. Western blotting was performed to detect the expression of P-glycoprotein (P-gp) and the cell cycle related proteins Cyclin D1 and p21(WAF1/CIP1).
  
  
  RESULTS
  Low concentrations of celecoxib (<20 µmol/L) produced no obvious effect on the proliferation of the cells. But at 10 µmol/L, celecoxib significantly enhanced the toxicity of VCR in a time-dependent manner, and the combined treatments for 24, 48, and 72 h caused growth inhibition rates of (37.53∓2.05)%, (46.67∓3.17)% and (54.02∓1.53)%, respectively, significantly higher than those following treatments with celecoxib or VCR alone (P<0.01). Compared with the cells treated with VCR alone , the cells with combined treatments showed a significantly increased cell percentage in G0/G1 phase [(56.08∓0.46)%] with decrease percentages in S phase [(22.83∓0.20)%] and G2/M phase [(21.09%∓0.66)%]. The combined treatment also significantly down-regulated cyclin D1, up-regulated p21(WAF1/CIP1), and reduced P-gp expressions in the cells.
  
  
  CONCLUSIONS
  Celecoxib enhances the chemosensitivity of KB/VCR cells by down-regulating P-gp expression, which is partially mediated by modification of cyclin D1 and p21(WAF1/CIP1) to result in cell cycle arrest.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. liaowenxiao2011@163.com
authors.forename: Wenxiao
authors.initials: W
authors.lastname: Liao
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Yan
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huang
authors.forename: Weizhong
authors.initials: W
authors.lastname: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007624:KB Cells; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011720:Pyrazoles; D013449:Sulfonamides; D019938:Cyclin D1; D000068579:Celecoxib